Orsha was first mentioned in 1067 as Rsha (Template:Lang-Ruthenian), making it one of the oldest towns in Belarus. The town was named after the river, which was originally also named Rsha, probably from a Baltic root *rus 'slowly flowing.'[2]

In 1555, Mikołaj "Czarny" Radziwiłł founded a Calvinist (Protestant) order in Orsha, one of the first in the Belarusian lands. From the sixteenth to eighteenth centuries Orsha was a notable religious centre, with dozens of Orthodox, Protestant and Catholic churches and orders. The town was also home to a large Jewish population.

During the First World War, the city was occupied by German forces in February–October 1918. From February 2, 1919, Orsha became a part of Homyel region (Vitebsk region, 1920) of Soviet Russia. After the formation of the Soviet Union, it was transferred to the Byelorussian SSR in 1924.

The population before World War II was about 37,000. The city was occupied by Germany on July 16, 1941. The occupiers founded several concentration camps in the city, where an estimated 19,000 people were killed.[citation needed]

There is a widespread Soviet myth of Katyusha Katyusha multiple rocket launcher's maiden attack of July 14, 1941 at Orsha, destroying a station with several supply trains. This legend obviously conflicts the fact that Orsha remained at the hands of the Soviet Army on July 14 and through July 15, 1941. And even on July 16, 1941 the German troops were unlikely to invade Orsha aboard their supply trains. Thus, had the Katyusha’s rockets fallen on any supply trains on July 16, 1941 those would have been the Soviet trains unable to have left Orsha railroad station. See Russian Wikipedia's article "Гвардейские реактивные минометы" ("Guards Mortars"). The multiple rocket launchers were top secret in the beginning of World War II and any records of their actions in July 1941 were forbidden, which fact led to numerous rumors and myths. The Soviets encouraged and co-ordinated undercover anti-fascist resistance groups, and one of the most famous was a partisan brigade under the command of Kanstantsin Zaslonau (Konstantin Zaslonov), operating from the Orsha train depot. His group planted ninety-three bombs on German trains in just three months. After March 1942, he went in hiding in the forests, where he and his group continued guerilla warfare. He was killed in action on November 14, 1942. Soviet troops liberated Orsha on June 27, 1944.

Orsha became an important transportation center after the construction of a Dnieper River port. The coming of railway lines in the second half of the nineteenth century greatly contributed to the city growth:

Today, Orsha is a major railway node where the Minsk–Moscow crosses the northern Viciebsk line, which branches south to Mogilev and Kryčaŭ. All trains from Moscow and Saint-Petersburg bound for Western Europe pass through Orsha.

The city is also a junction of the important motorways: The M1 (E30) Moscow-Brest and the M8/M20 (E95) Saint Petersburg - Odessa.

OSGOEINT recently reported on the 571st Aircraft Repair Plant (ARP) located at Orsha (also called Bolbasovo) Airfield. Accordingly, the 571st ARP repairs Mi-8-17 HIP, Mi-24-35 HIND, as well as the Tu-134 CRUSTY and possibly the IL-76 CANDID. The report goes on to mention recent investment agreements with the Ukraine where private firms plan on providing $12 million to finance facility upgrades during the 2012-2016 period. Press reporting states that the investors plan on building a modern warehouse terminal as well as office buildings for customs services, banking, and a leasing company.[6]

Recently, a high rate of oncological diseases attracted attention to this city. Before 1987 there were less than 100 new cancer patients registered each year. Since then the number grew fivefold, with more than 500 new patients registered per year as of 2004. The biggest growth was registered in 2003–04 (178%). This was widely reported in independent media, but Belarusian officials are silent about the alarming health situation and possible reasons for this high cancer rate. Two possible factors mentioned in the independent media are old Soviet military installations in Orsha, and the Chernobyl disaster.